Pivotal factors associated with the immunosuppressive tumor microenvironment and melanoma metastasis

Zhang, Chuan; Dang, Dan; Cong, Lele; Sun, Hongyan; Cong, Xianling

doi:10.1002/cam4.3963

Cited by 37 publications

(30 citation statements)

References 52 publications

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“…Since miRNAs’ expression information is absent from our dataset, our conclusions cannot include the direct association with the miRNAs. In line with several previous reports that have highlighted the importance of immune function in the process of melanoma metastasis and ICB response [ 52 , 53 , 54 , 55 ], our results show a profound influence of the dysregulation of these non-coding RNAS (ncRNAs) on the activation or inhibition of key anti-tumor immunological processes, such as the Th1, natural-killer cell-signaling, T-cell receptor signaling or the PD-1–PD-L1 cancer immunotherapy pathways. Interestingly, the expression perturbation of the responders was associated with an increasing expression of PD-1 and PD-L1 (CD274).…”

Section: Discussionsupporting

confidence: 92%

“…Two of the main molecules highlighted by the ceRNA network ( Figure 5 a) are TNF and IFNG. Recently, the overexpression of TNF, IFNG and IL2, among other molecules, have been reported as key molecules that may enhance melanoma progression through activating the JAK–STAT signaling pathway [ 55 ]. Moreover, other studies indicate that both TNF and IFNG are directly linked with the high density, T-cell infiltration and cytotoxicity of cytotoxic T-cell (CTL) functions [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

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Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma

et al. 2022

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Cutaneous melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40–65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expressions as pre-treatment predictors of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma

et al. 2022

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“…Two of the main molecules highlighted by the ceRNA network (Figure 5a) are TNF and IFNG. Recently, the overexpression of TNF, IFNG and IL2 among other molecules have been reported as key molecules that may enhance melanoma progression through activating the JAK-STAT signaling Pathway [70]. Moreover, other studies indicate that both TNF and IFNG are directly linked with high density and T cell infiltration and Cytotoxicity of cytotoxic T cells function (CTL) [71].…”

Section: Discussionmentioning

confidence: 99%

Association of Circular RNA and Long Noncoding RNA Dysregulation to Clinical Response to Immunotherapy in Cutaneous Metastatic Melanoma

Oliver¹,

Onieva²,

Garrido-Barros³

et al. 2022

Preprint

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Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

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“…Two previous integrated analysis studies reported that RBM26-AS1 acts as a ceRNA in high-glucose-induced human retinal endothelial cells ( Cao et al, 2020 ) and pancreatic cancer ( Liu et al, 2020 ). Furthermore, in melanoma, RBM26-AS1 dysregulation has been found in CD4 memory T cells ( Zhang et al, 2021 ). It is noteworthy that the association between these three lncRNAs with ASD has been reported in this study for the first time; therefore, more research is required to confirm our findings.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder

Sabaie

Dehghani

Shiva

et al. 2021

Front. Mol. Biosci.

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Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

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Pivotal factors associated with the immunosuppressive tumor microenvironment and melanoma metastasis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 37 publications

References 52 publications

Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma

Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma

Association of Circular RNA and Long Noncoding RNA Dysregulation to Clinical Response to Immunotherapy in Cutaneous Metastatic Melanoma

Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder

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